This proposal addresses NINDS Research topic l.E.1, "Development of objective methods for quantitative assessment of pain and sensory conduction mechanisms." The pathways of pain transmission have a major impact on human behavior. They are normally protective, but too often become pathological. The transition or re-routing from one to the other is poorly understood. It is proposed to construct a tool for the dissection of pain pathways, in order to delineate more precisely the transmission of normal and pathological pain. The major nociceptor classes in the adult dorsal root ganglion are the nerve growth factor (NGF)-responsive neurons that express substance P and CGRP, and the IB4 lectin-binding neurons that are TrkA (NGF)-receptor-negative. Methods will be carried out to specifically eliminate individually these neuronal types using targeted toxins directed to TrkA in one case and IB4-binding moieties in the other. This will allow study in vitro and in vivo of the two neuronal types in an environment independent of each other. These tools will result in a better understanding of nociception mechanisms and possibly result in new therapies for some chronic pain states. PROPOSED COMMERCIAL APPLICATIONS: This proposal seeks to develop an immunolesioning tool for neurons that express the TrkA receptor, the signal transduction receptor for NGF. The proposed tool would give researchers a new, innovative method for probing the function of NGF-responsive cells in pain transmission. The commercial potential spans from the innovative research tool for neuroscience to a possible therapeutic in the treatment of pain.